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SAN FRANCISCO – according to the results of a new genetic analysis of prostate cancers in men in the Health Professionals Follow Up Study.
A previous analysis from the Health Professionals Follow Up Study published in 2015 showed no difference in the risk of lethal prostate cancer for those who began using statins after diagnosis of their tumors.
A genetic analysis of these lethal cases revealed that patients taking long-term statins had a lower incidence of phosphatase and tensin homolog (PTEN)–null cancers, which are associated with worse outcomes. Integrating molecular and epidemiologic data, PTEN and PI3K (phosphatidylinositol) signaling and inflammation and immune activation appear to be two potential mechanisms contributing to this association.
Genetic analysis of normal prostate tissue also showed unique traits among statin users. “We found that the top ten pathways that came up were almost all involved in inflammation or immune activation, and we found those differences only in tumor and adjacent normal prostate tissue. We didn’t see any pathways that were differentially expressed by statin use within the tumor tissue itself,” said Emma Allott, PhD, who presented the research at a poster session at the annual meeting of the American Urological Association.
An association between statin use and improved survival was first described in a 2006 study based on results from the Health Professionals Follow Up Study. Since then, “we’ve been generating molecular data on cancers that developed in statin users and nonusers,” said Dr. Allott of the University of North Carolina, Chapel Hill.
Of the 5,792 prostate cancer diagnoses, 17% were advanced cases, defined as stage T3b or more, having spread to lymph nodes or metastasized, or lethal; 13% were lethal, 46% were positive for the ERG oncogene, and 14% were PTEN-null. “Statin use was associated with a lower risk of PTEN-null prostate cancer, so that seems to drive some of the reduced association with lethal disease,” said Dr. Allott.
There was no association between lethality and ERG-positive or ERG-negative status. Those who used statins for more than 5 years were less likely to have a PTEN-null tumor (hazard ratio, 0.42; 95% confidence interval, 0.20-0.90) but not more likely to have a PTEN-positive tumor (HR, 1.18; 95% CI, 0.95-1.46).
Compared with never users, long-term statin users also were less likely to have advanced prostate cancer (multivariate analysis, HR, 0.62; 95% CI, 0.45-0.85) as well as lethal prostate cancer (HR, 0.52; 95% CI, 0.35-0.78).
The researchers conducted a gene set enrichment analysis in statin users and found an enrichment of T-cell, B-cell, and PI3K signaling in tumor-adjacent normal prostate tissue, as well as other changes. “We think maybe there’s a microenvironment inflammation component to the mechanism through which statins are associated with lower risk of lethal prostate cancer,” said Dr. Allott.
The molecular data could identify patient subgroups that could benefit from statins. Dr. Allott said that is the goal, but it will take time. “That’s more obviously translatable to the clinic, but we don’t yet have enough data in this cohort to look at that.”
SOURCE: Allott E et al. AUA 2018, Abstract MP21-01.
SAN FRANCISCO – according to the results of a new genetic analysis of prostate cancers in men in the Health Professionals Follow Up Study.
A previous analysis from the Health Professionals Follow Up Study published in 2015 showed no difference in the risk of lethal prostate cancer for those who began using statins after diagnosis of their tumors.
A genetic analysis of these lethal cases revealed that patients taking long-term statins had a lower incidence of phosphatase and tensin homolog (PTEN)–null cancers, which are associated with worse outcomes. Integrating molecular and epidemiologic data, PTEN and PI3K (phosphatidylinositol) signaling and inflammation and immune activation appear to be two potential mechanisms contributing to this association.
Genetic analysis of normal prostate tissue also showed unique traits among statin users. “We found that the top ten pathways that came up were almost all involved in inflammation or immune activation, and we found those differences only in tumor and adjacent normal prostate tissue. We didn’t see any pathways that were differentially expressed by statin use within the tumor tissue itself,” said Emma Allott, PhD, who presented the research at a poster session at the annual meeting of the American Urological Association.
An association between statin use and improved survival was first described in a 2006 study based on results from the Health Professionals Follow Up Study. Since then, “we’ve been generating molecular data on cancers that developed in statin users and nonusers,” said Dr. Allott of the University of North Carolina, Chapel Hill.
Of the 5,792 prostate cancer diagnoses, 17% were advanced cases, defined as stage T3b or more, having spread to lymph nodes or metastasized, or lethal; 13% were lethal, 46% were positive for the ERG oncogene, and 14% were PTEN-null. “Statin use was associated with a lower risk of PTEN-null prostate cancer, so that seems to drive some of the reduced association with lethal disease,” said Dr. Allott.
There was no association between lethality and ERG-positive or ERG-negative status. Those who used statins for more than 5 years were less likely to have a PTEN-null tumor (hazard ratio, 0.42; 95% confidence interval, 0.20-0.90) but not more likely to have a PTEN-positive tumor (HR, 1.18; 95% CI, 0.95-1.46).
Compared with never users, long-term statin users also were less likely to have advanced prostate cancer (multivariate analysis, HR, 0.62; 95% CI, 0.45-0.85) as well as lethal prostate cancer (HR, 0.52; 95% CI, 0.35-0.78).
The researchers conducted a gene set enrichment analysis in statin users and found an enrichment of T-cell, B-cell, and PI3K signaling in tumor-adjacent normal prostate tissue, as well as other changes. “We think maybe there’s a microenvironment inflammation component to the mechanism through which statins are associated with lower risk of lethal prostate cancer,” said Dr. Allott.
The molecular data could identify patient subgroups that could benefit from statins. Dr. Allott said that is the goal, but it will take time. “That’s more obviously translatable to the clinic, but we don’t yet have enough data in this cohort to look at that.”
SOURCE: Allott E et al. AUA 2018, Abstract MP21-01.
SAN FRANCISCO – according to the results of a new genetic analysis of prostate cancers in men in the Health Professionals Follow Up Study.
A previous analysis from the Health Professionals Follow Up Study published in 2015 showed no difference in the risk of lethal prostate cancer for those who began using statins after diagnosis of their tumors.
A genetic analysis of these lethal cases revealed that patients taking long-term statins had a lower incidence of phosphatase and tensin homolog (PTEN)–null cancers, which are associated with worse outcomes. Integrating molecular and epidemiologic data, PTEN and PI3K (phosphatidylinositol) signaling and inflammation and immune activation appear to be two potential mechanisms contributing to this association.
Genetic analysis of normal prostate tissue also showed unique traits among statin users. “We found that the top ten pathways that came up were almost all involved in inflammation or immune activation, and we found those differences only in tumor and adjacent normal prostate tissue. We didn’t see any pathways that were differentially expressed by statin use within the tumor tissue itself,” said Emma Allott, PhD, who presented the research at a poster session at the annual meeting of the American Urological Association.
An association between statin use and improved survival was first described in a 2006 study based on results from the Health Professionals Follow Up Study. Since then, “we’ve been generating molecular data on cancers that developed in statin users and nonusers,” said Dr. Allott of the University of North Carolina, Chapel Hill.
Of the 5,792 prostate cancer diagnoses, 17% were advanced cases, defined as stage T3b or more, having spread to lymph nodes or metastasized, or lethal; 13% were lethal, 46% were positive for the ERG oncogene, and 14% were PTEN-null. “Statin use was associated with a lower risk of PTEN-null prostate cancer, so that seems to drive some of the reduced association with lethal disease,” said Dr. Allott.
There was no association between lethality and ERG-positive or ERG-negative status. Those who used statins for more than 5 years were less likely to have a PTEN-null tumor (hazard ratio, 0.42; 95% confidence interval, 0.20-0.90) but not more likely to have a PTEN-positive tumor (HR, 1.18; 95% CI, 0.95-1.46).
Compared with never users, long-term statin users also were less likely to have advanced prostate cancer (multivariate analysis, HR, 0.62; 95% CI, 0.45-0.85) as well as lethal prostate cancer (HR, 0.52; 95% CI, 0.35-0.78).
The researchers conducted a gene set enrichment analysis in statin users and found an enrichment of T-cell, B-cell, and PI3K signaling in tumor-adjacent normal prostate tissue, as well as other changes. “We think maybe there’s a microenvironment inflammation component to the mechanism through which statins are associated with lower risk of lethal prostate cancer,” said Dr. Allott.
The molecular data could identify patient subgroups that could benefit from statins. Dr. Allott said that is the goal, but it will take time. “That’s more obviously translatable to the clinic, but we don’t yet have enough data in this cohort to look at that.”
SOURCE: Allott E et al. AUA 2018, Abstract MP21-01.
REPORTING FROM THE AUA ANNUAL MEETING
Key clinical point: Researchers hope that genetic analyses could eventually point to prostate cancer patients who might benefit from statin use.
Major finding: Long-term statin users had lower odds of having a pTEN-null tumor (hazard ratio, 0.42), which is associated with worse outcomes.
Study details: Retrospective analysis of 5,792 diagnoses of prostate cancer among 44,076 men.
Disclosures: The study was funded by the Irish Cancer Society, the John Fitzpatrick Fellowship, and the National Cancer Institute. Dr. Allott reported no relevant financial relationships.
Source: Allott E et al. AUA 2018, Abstract MP21-01.